MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.

Autor: Andrea Turner, Liang-Cheng Li, Tania Pilli, Lixia Qian, Elizabeth Louise Wiley, Suman Setty, Konstantin Christov, Lakshmy Ganesh, Ajay V Maker, Peifeng Li, Prasad Kanteti, Tapas K Das Gupta, Bellur S Prabhakar
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: PLoS ONE, Vol 8, Iss 2, p e56817 (2013)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0056817
Popis: The Map kinase Activating Death Domain containing protein (MADD) isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.
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